Abstract

Using extra- and intracellular recording techniques, we investigated the epileptiform activity induced by low concentrations (5 and 10 microM) of bath-applied 4-aminopyridine (4-AP) in the CA3 subfield of rat hippocampal slices. We also studied the effects of 4-AP on the excitatory and inhibitory synaptic conductance changes in CA3 neurons produced by mossy fiber stimulation. Low concentrations of 4-AP induced spontaneously occurring epileptiform discharges at extracellular potassium concentrations between 1 and 10 mM. In contrast, picrotoxin and bicuculline produced spontaneous epileptiform discharges at extracellular potassium concentrations between 5 and 10 mM. The paroxysmal depolarizing shift (PDS) induced by 4-AP was also investigated. At potentials between -40 and -10 mV, the waveform of the PDS consisted of a depolarizing component enveloped by a hyperpolarizing component. The amplitude of the depolarizing component of the PDS was a monotonic function of the membrane potential, and the mean measured reversal potential was -25.7 mV. Under voltage-clamp conditions, the measured conductance associated with the depolarizing component of the PDS averaged 110 nS, with a reversal potential of -14.1 mV. Application of 5 microM 4-AP produced an increase in the inhibitory synaptic conductance change calculated from currents measured 15 ms following mossy fiber stimulation. The mean value increased from 35.2 to 58.1 nS (P less than 0.05) without a significant change in reversal potential. A concentration of 10 microM 4-AP also produced an increase in this inhibitory synaptic conductance change (from 53.3 to 66.3 nS, P less than 0.05) but caused a significant depolarization of the reversal potential (from -66.5 to -61.6 mV, P less than 0.05). This change in reversal potential may reflect a prolongation of the excitatory synaptic currents produced by 4-AP that contributes to the current measured 15 ms from the stimulus. Following application of either 5 or 10 microM 4-AP, there were no significant changes in the resting potential or input resistance of the neurons studied. Application of 5 microM 4-AP also significantly increased the amplitude of the measured excitatory synaptic conductance change produced by mossy fiber stimulation (from 27.9 to 44.1 nS, P less than 0.05) without producing a change in the reversal potential. In 5 of 21 neurons studied, a long-lasting outward synaptic current was present at holding potentials near rest following mossy fiber stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

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Cover: Genetically labeled inhibitory cortical interneurons in a triple transgenic mouse, in which all parvalbumin-containing, fast-spiking interneurons express tdTomato (red), and a subset of somatostatin-containing interneurons express green fluorescent protein (green). Parvalbumin and somatostatin are clearly expressed in nonoverlapping subsets of neurons; however, the two subsets communicate synaptically by forming inhibitory synapses on each other. This mutual inhibition generates millisecond-precision spike synchrony in connected heterotypic pairs, as illustrated in the inset. Precise synchrony is also evident in homotypic pairs, where it can be driven by chemical synapses, by electrical coupling, or by both. From Hu H, Agmon A. Properties of precise firing synchrony between synaptically coupled cortical interneurons depend on their mode of coupling. J Neurophysiol; published ahead of print May 13, 2015, doi:10.1152/jn.00304.2015.